Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chlorid...Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.展开更多
Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase an...Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (SERT), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating SERT and N/K ATPase receptors. Minimum energy conformers of SERT antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a SERT-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes.展开更多
Sweeteners and flavor enhancers are food additives widely used in industry, respectively, to add sweetness and flavor to foods. However, the presence of these substances is often criticized by consumers for their effe...Sweeteners and flavor enhancers are food additives widely used in industry, respectively, to add sweetness and flavor to foods. However, the presence of these substances is often criticized by consumers for their effects on health. What’s more, some scientific studies link these substances to certain pathologies. To guarantee food safety, competent authorities should have food standards based on risk analysis using consistent, reliable data. However, in developing countries, such data is often weak or non-existent. The aim of this study is therefore to carry out a pilot survey to establish the profile of sweeteners and flavour enhancers present in industrial food products marketed in Senegal. The methodology consisted of sampling various food products sold on the Senegalese market, based on analysis of labels containing information on ingredients, including additives. The investigation involved nine stores, one supermarket and 5 mini-markets in Dakar. The results showed the presence of 6 taste enhancers in food products, the most frequent being sodium L-monoglutamate (E621), inosinate (E631) and disodium guanylate (E627). Solid broths are the foodstuffs with the highest number of taste exhalters. As for sweeteners, 12 substances were identified, the most frequent being acesulfame potassium (E950), aspartame (E951), sucralose (E955) and saccharin (E954). Given the potential health risks associated with the consumption of these food additives, their control and monitoring on the market should be a priority for the competent authorities.展开更多
基金supported by a grant from Guangzhou Medical University,No.2008C24
文摘Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.
文摘Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (SERT), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating SERT and N/K ATPase receptors. Minimum energy conformers of SERT antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a SERT-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes.
文摘Sweeteners and flavor enhancers are food additives widely used in industry, respectively, to add sweetness and flavor to foods. However, the presence of these substances is often criticized by consumers for their effects on health. What’s more, some scientific studies link these substances to certain pathologies. To guarantee food safety, competent authorities should have food standards based on risk analysis using consistent, reliable data. However, in developing countries, such data is often weak or non-existent. The aim of this study is therefore to carry out a pilot survey to establish the profile of sweeteners and flavour enhancers present in industrial food products marketed in Senegal. The methodology consisted of sampling various food products sold on the Senegalese market, based on analysis of labels containing information on ingredients, including additives. The investigation involved nine stores, one supermarket and 5 mini-markets in Dakar. The results showed the presence of 6 taste enhancers in food products, the most frequent being sodium L-monoglutamate (E621), inosinate (E631) and disodium guanylate (E627). Solid broths are the foodstuffs with the highest number of taste exhalters. As for sweeteners, 12 substances were identified, the most frequent being acesulfame potassium (E950), aspartame (E951), sucralose (E955) and saccharin (E954). Given the potential health risks associated with the consumption of these food additives, their control and monitoring on the market should be a priority for the competent authorities.
